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OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.
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Animals , Mice , Autophagy , Calcium/metabolism , Chondrocytes , Endoplasmic Reticulum/metabolism , Endoribonucleases/pharmacology , Homeostasis , Inositol , Mice, Knockout , Protein Serine-Threonine Kinases , RNA, Messenger/metabolism , Sirolimus/pharmacology , Tunicamycin/pharmacologyABSTRACT
OBJECTIVE Cerebral ischemia or ischemic stroke is due to insufficient blood supply to the brain, which causes hypoxia or ischemia in some areas. This work aimed to quantify the minerals and heavy metals in Qishiwei Zhenzhu pill in vivo and in vitro, analyze its effect on the types and abundance of intestinal flora, and study its mechanism on inflammation and apoptosis pathways as a treatment for cerebral ischemia. METHODS Microwave digestion and induc?tively coupled plasma mass spectrometry (ICP-MS) were used to determine the minerals and heavy metals in 10 batches of Qishiwei Zhenzhu pill in vitro. With the use of the middle cerebral artery obstruction (MCAO) model, ICP-MS was applied to determine the content of minerals and heavy metals in hepatic portal vein blood, abdominal aortic blood, brain, liver, kidney, hair, urine and feces at different time periods. On this model, the ileum, cecum, and colon tissues were tested for intestinal pathology, and 16S rRNA was used for sequencing. Species taxonomy, α diversity, and spe?cies microbial composition and structure analysis were also performed. Polymerase chain reaction and Western blotting were employed to determine the mRNA and protein expression of p38 MAPK, caspase-3, IL-1β and TNF-α in the isch?emic brain tissues of rats. RESULTS The average content of heavy metals in the 10 batches of Qishiwei Zhenzhu pill samples is in the descending order Hg>Cu>Pb. Significant differences in the metal elements are found among Qishiwei Zhenzhu pill from different manufacturers but not among the different batches of the same manufacturer. An extremely low content of heavy metals are absorbed into the blood or accumulated in the brain, liver, kidney, and other tissues. Stool is the main excretion route of minerals and heavy metals from Qishiwei Zhenzhu pill. This medicine helps repair the intestinal mucosa in MCAO rats. At the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the intestinal flora of rats with cerebral ischemia. At the genus level, it can adjust the abundance of Escherichia Shigella. At the species level, it can adjust the abundance of Lactobacillus yoelii and Lactobacillus reuteri. Cluster classification results show that Qishiwei Zhenzhu pill can improve the intestinal flora of rats with cerebral ischemia, reduce the mRNA and protein expression of caspase-3 and IL-1βin rat brain tissues, and have a tendency to decrease the mRNA expres?sion of p38 MAPK and TNF-α. CONCLUSION Quantifying the minerals and heavy metals in Qishiwei Zhenzhu pill in vivo and in vitro will help improve their quality standards. Minerals and heavy metals are mainly excreted in feces, accumu?late in extremely low levels in various tissues, and do not damage the intestinal mucosa. The effective material basis of Qishiwei Zhenzhu pill in treating cerebral ischemia may be related to their Li, Cr, and Cd elements. These pills can improve the environment of intestinal flora, and their mechanism of treatment for cerebral ischemia may be related to the down-regulation of IL-1βinflammatory factor and inhibition of cell apoptosis.
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Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (
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OBJECTIVE@#To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants.@*METHODS@#Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results.@*RESULTS@#Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age T mutation tend to have mild conditions.
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Female , Humans , Infant , Infant, Newborn , China/epidemiology , Genetic Testing , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase Deficiency/genetics , Infant, Premature , MutationABSTRACT
Objective: To establish a UPLC fingerprint method and a method for the content determination of 3,5-O-dicaffeoylquinic acid of Aucklandiae Radix, and provide a comprehensive evaluation of the drug from different habitats. Methods: UPLC analysis was performed on a YMC Trait C18 (100 mm × 2.1 mm, 1.9 μm), with a mobile phase consisting of acetonitrile-0.05% phosphoric acid at the flow rate of 0.30 mL/min. The fingerprint detection wavelength was 254 nm and the content determination detection wavelength of 3,5-O-dicaffeoylquinic acid was 327 nm, meanwhile, the column temperature was controlled at 30 ℃. Similarity analysis, hierarchical clustering analysis, and principal component analysis were undertaken to investigate the fingerprints of 13 batches of Aucklandiae Radix. Results: UPLC fingerprint of Aucklandiae Radix was established and eight common peaks were designated. The results showed that the quality of the batches of samples were not stable. Samples collected from the same region and different regions both had certain differences, as well as the content determination of 3,5-O-dicaffeoylquinic acid. Conclusion: The proposed method offered a fast, holistic, and effective method for the quality control of Aucklandiae Radix.
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Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids, cathayanalactones A-F (1-6), together with seven analogues (7-13). Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses. Compounds 1, 2, 3, 7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.
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Objective To understand the clinical characteristics and changes in laboratory indicators of patients died of visceral leishmaniasis (VL).Methods Clinical data of 4 patients died of VL in Beijing Friendship Hospital from January 2013 to June 2018 were analyzed, differences in laboratory indicators were compared.Results Disease course of 4 cases of VL ranged from3 to 12 months, all patients had multiple organ damage, including 3 cases with hepatomegaly and splenomegaly, 2 cases with central nervous system damage.IgG antibodies of leishmania were positive in 4 patients, Leishman-Donovan body was found in bone marrow smears.Routine peripheral blood test results in 4 patients decreased significantly, albumin decreased significantly and globulin increased;level of serum sodium ion in 4 patients was lower than 135 mmol/L.Conclusion Long disease course, multiple organ damage, involvement of central nervous system, significant reducing in peripheral blood routine test results, hypoproteinemia, and hyponatremia in patients with VL all indicate poor prognosis and high mortality.
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OBJECTIVE@#To compare the corneal biomechanical properties among keratoconus, subclinical keratoconus and normal corneas by using CorVis ST, and to estimate the effect of these biomechanical indices in discriminating keratoconus and subclinical keratoconus from normal.@*METHODS@#A total of 76 eyes of 67 subjects were enrolled and divided into three groups. Keratoconus group included 24 eyes from 17 patients, subclinical keratoconus group included 12 eyes from 12 patients and normal group included 40 normal eyes from 40 subjects．All the eyes were assessed with CorVis ST and ten biomechanical parameters, intraocular pressure (IOP) and central corneal thickness (CCT) were obtained from this machine. The discrimination of biomechanical characteristic of the three groups based on the all indices was reflected by discriminant analysis and the Fisher discriminant function was established.@*RESULTS@#The values of corneal biomechanics of keratoconus, subclinical keratoconus, normal eyes were increased in sequence, except for three indices: the second applamation time (A2T), time taken to reach highest concavity (HCT) and maximum corneal velocity during the first applanation (Vin). Three sets of data were among a statistically significant difference (P<0.05). There were statistically significant differences (P<0.05) between any two groups by comparing with such two indices: radius value of central concave curvature at highest concavity (HCR) and CCT. The grades of the three groups were obvious, evaluated by the discriminant function. The accuracy of reevaluation was 85% by validation method. The biggest contribution of indices in discriminant function was given by such four indices in sequence: CCT, HCR, maximum deformation amplitude of highest concavity (HCDA) and maximum corneal velocity during the second applanation (Vout).@*CONCLUSION@#The corneal biomechanical properties of keratoconus and subclinical keratoconus were decreased compared with normal eyes. The biomechanical parameters based on CorVis ST showed a good performance for discriminating among keratoconus, subclinical keratoconus and normal corneas.
Subject(s)
Humans , Biomechanical Phenomena , Cornea , Discriminant Analysis , Keratoconus , Tonometry, OcularABSTRACT
Rhododendron molle G. Don, belonging to the Ericaceae family, is a traditional Chinese medicinal plant with a wide spectrum of pharmacological effects. This paper aimed to review the phytochemistry, pharmacology and toxicology of R. molle, and to discuss the tendency of future investigations on this plant. A systematic review of literature about R. molle was carried out using resources including classic books about Chinese herbal medicine, and scientific data bases including CNKI, Pubmed, SciFinder, Scopus, and Web of Science. Over 67 compounds, including diterpenes, triterpenes, flavonoids, and lignans, had been extracted and identified from R. molle. The extracts/monomers isolated from the root, flower and fruits of this plant were used as effective agents for treating pains, inflammatory diseases, hypertension, and pest, etc. In addition, diterpenes, such as rhodojaponin III, were considered as the toxic agents associated with the toxicities of this plant. These findings will be significant for the discovery of new drugs from this plant and full utilization of R. molle.
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Animals , Humans , Medicine, Chinese Traditional , Molecular Structure , Phytotherapy , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Toxicity , Plants, Medicinal , Rhododendron , ChemistryABSTRACT
Artesunate (AS), a famous derivative of the artemisinin, is the basic treatment globally for mild to severe malaria infection due to the prominent advantages such as high efficiency, fast effect, low toxicity and not easy to produce resistance. More and more research reports have shown that AS and its active metabolites dihydroartemisinin (DHA) had various bioactivities in addition to antimalarial activity, attracting researchers to further study its new pharmacological effects in order to explore new use of the old drug. A comprehensive understanding of the pharmacokinetic characteristics of AS will be conducive to the further development of new pharmacological actions and clinical application of AS. Therefore, this paper would review the absorption, distribution, metabolism and excretion of AS , as well as the pharmacokinetics characteristics of AS and DHA after clinical administration of AS by intravenous (IV), intramuscular (IM), oral or rectal routes. The process and pharmacokinetic parameters of AS and DHA were compared between healthy volunteers, malaria patients, and special populations (children, women). Meanwhile, the research progress on pharmacological effects of AS and active metabolite DHA such as anti-tumor, anti-inflammatory, anti septic, antiangiogenic, anti-fibrosis and immunoregulation activities would be also reviewed, hoping to provide a theoretical basis for the further development and utilization of AS and its metabolites.
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Humans , Antimalarials , Pharmacokinetics , Pharmacology , Artesunate , Pharmacokinetics , Pharmacology , ResearchABSTRACT
BACKGROUND: The thermo-sensitive composite hydrogels have gained increasing interest in bone regeneration domain due to their biomimetic extracellular matrix (ECM) structure, good biocompatibility, minimal invasive performance and in situ molding. OBJECTIVE:To prepare a thermo-sensitive injectable alginate/α-tricalcium phosphate (α-TCP)/collagen I (Alg/TCP/Col) composite hydrogel and explore its characterization. METHODS:Ca-carrying interdigitation-fusion vesicles (Ca-IFVs) were prepared. The liposomes carrying the optimal concentration of calcium ions were selected for the following experiments by investigating their encapsulation efficiency and drug loading rate. Alg/TCP/Col precursor solution (Alg or Alg/TCP precursor solution) was mixed with Ca-IFVs at 37℃ in different proportions (5, 10, 15, 20) to prepare thermosensitive hydrogels. The structure, rheology behavior, volume swelling ratio, and mechanical properties of the composite hydrogel were observed. MC3T3-E1 cells were co-cultured with Alg/TCP/Col, Alg, and Alg/TCP hydrogels, respectively. Then, morphology of the cells was observed by confocal microscopy at 1, 3, 7 days after co-culture. RESULTS AND CONCLUSION:(1) The pore size of the freeze-dried hydrogel was 50-100 μm, and TCP particles uniformly adhered to the surface of the Alg/TCP hydrogel surface. The Alg/TCP/Col hydrogel was a dense aggregate with collagen fibers in contrast to the Alg/TCP hydrogel. (2) The Alg/TCP/Col hydrogel exhibited a suitable phase transition temperature (Tm) between 35-39℃. (3) The volume swelling ratio of the hydrogel was increased with the increase of Ca-IFVs size. When the α-TCP complex was added into the Alg/TCP hydrogel, the swelling ratio decreased slightly. Alg/TCP/Col hydrogel exhibited a higher swelling ratio than the Alg/TCP hydrogel. (4) When the mixture ratio of precursor solution to liposome was 10, the compressive modulus of Alg/TCP/Col hydrogel and Alg/TCP hydrogel was significantly higher than that of the Alg hydrogel (P<0.05). (5) When the mixture ratio of precursor solution to liposome was 10, round MC3T3-E1 cells were observed on the Alg hydrogel; the cells on the surface of the Alg/TCP hydrogel were scattered and tended to extend; the cells on the surface of the Alg/TCP/Col hydrogel had a stress-extended morphology, and grew into the hydrogel, and meanwhile, the cell number increased significantly. To conclude, the liposome-mediated Alg/TCP/Col has good mechanical properties and cytocompatibility.
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OBJECTIVES@#To set up ELISA for detection of atrazine with high precision.@*METHODS@#The reaction condition of indirect-ELISA was optimized, including atrazine-ovalbumin(AT-OVA) concentration and primary antibody concentration, organic solvent, goat anti-rat immunoglobin G-horseradish peroxidase(IgG-HRP) concentration. The actual samples were detected by the ELISA method established in our laboratory. Then the ELISA method was compared with the HPLC.@*RESULTS@#The specification curve of indirect-ELISA was set up after optimization. The relation coefficient R=0.9958. The limit of detection (LOD) was 1.972 ng/ml. The percent recovery of the actual samples was in range of 80%~120%. The ELISA detection sensitivity was higher than the HPLC in the range of 0 ng/ml~6 ng/ml atrazine.@*CONCLUSIONS@#The ELISA to detect atrazine has good specificity and high precision. And it can be applied in testing real atrazine samples replacing of the large-scale instrument.
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Animals , Atrazine , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Sensitivity and SpecificityABSTRACT
Rhododendron molle G. Don, belonging to the Ericaceae family, is a traditional Chinese medicinal plant with a wide spectrum of pharmacological effects. This paper aimed to review the phytochemistry, pharmacology and toxicology of R. molle, and to discuss the tendency of future investigations on this plant. A systematic review of literature about R. molle was carried out using resources including classic books about Chinese herbal medicine, and scientific data bases including CNKI, Pubmed, SciFinder, Scopus, and Web of Science. Over 67 compounds, including diterpenes, triterpenes, flavonoids, and lignans, had been extracted and identified from R. molle. The extracts/monomers isolated from the root, flower and fruits of this plant were used as effective agents for treating pains, inflammatory diseases, hypertension, and pest, etc. In addition, diterpenes, such as rhodojaponin III, were considered as the toxic agents associated with the toxicities of this plant. These findings will be significant for the discovery of new drugs from this plant and full utilization of R. molle.
Subject(s)
Animals , Humans , Medicine, Chinese Traditional , Molecular Structure , Phytotherapy , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Toxicity , Plants, Medicinal , Rhododendron , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To investigate the metabolism characteristics, to search for potential biomarkers associated with disease and to explore related metabolic pathways by analyzing the plasma metabolic profile of patients with chronic myelogenous leukemia (CML) through metabolomies.</p><p><b>METHODS</b>Twenty-six newly diagnosed CML patients in the First Affilated Hospital of Soochow University from February 2015 to April 2015, 26 allogeneic hematopoietic stem cell donors as healthy controls and 26 patients treated with tyrosine kinase inhibitors (TKI) to obtain the best efficacy as post-treatment controls were enrolled in this study. All the metabolites of plasma were extracted by Gas Chromatography-Mass Spectrometer(GC-MS) to collect metabolic fingerprint. Multivariate pattern recognition analysis and t test were combined to screen out the metabolic biomarkers at different time points. The receiver operating characteristic curve analysis was used to evaluate the clinical efficacy of metabolites, and the metabolic pathway analysis was performed.</p><p><b>RESULTS</b>Significantly different metabolite expression mode was found seen between CML and healthy control groups. Six changed metabolites in CML were confirmed by multivariate and variate statistical analyses. Compared with the healthy controls, the levels of tetradecanoic acid and glycerol were decreased, the lactic acid, myo-inositol, d-galactose and glycine in CML patients also increased (all VIP>1,P<0.05, AUC>0.7). The plasma metabolites in CML patients after treatment with tyrosine kinase inhibitors (TKI) showed a recovery trend toward to normal levels. The plasma metabolic pathways of CML were mainly related with galactose, pyruvate, glycerolipid, inositol phosphate and glycine, serine and threonine metabolism (all impact value>0.10).</p><p><b>CONCLUSION</b>Significant changes in plasma metabolite levels were found in CML patients. Metabolomics combined with multivariate pattern recognition analysis may be a new tool to assist diagnosis.</p>
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It is not scientific to explain that fried Fructus Hordei Germinatus is more effective than row Fructus Hordei Germinatus in resolving food stagnation from the aspects of amylase, tricine and other "active ingredients". In the present experiment, the contents of active ingredients including quercetin, tricine, kaempferol, catechin, ferulic acid and inactive ingredients including 5-hydroxymethyl furfural, acrylamide in frying process were determined by HPLC. The dynamic change rules of active ingredient and inactive ingredients in the frying process were investigated by HCA, PCA and PLS-DA analysis. The results showed that the Fructus Hordei Germinatus samples with different frying temperatures were classified into 4 groups by HCA and PCA analysis. PLS-DA analysis showed that frying temperature mainly impacted the contents of inactive ingredients including 5-hydroxymethyl furfural and acrylamide, with less effects on the contents of active ingredients. Simultaneously, with the increase of time in frying process, the content of 5-hydroxymethyl furfural was significantly increased from 2 min and became stable at 16 min, while the content of acrylamide was increased continuously from 18 min. Based on the variation of the contents of various ingredients, samples at different frying time were classified into 5 groups. The results showed that the content changes of "inactive ingredients" were closely related to the duration and degree of frying process, and the dynamic change rules of "inactive ingredients" can provide scientific basis for evaluating the frying process and elucidating the efficacy mechanism of Fructus Hordei Germinatus.
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The Aconiti Radix Cocta gel and Aconiti Radix Cocta combined with Paeoniae Radix Alba gel were administered to mice. Physiological saline was taken as perfusate. The perfusion rate was 2 μL•min⁻¹ and the microdialysis samples were collected every 0.5 h intervals for eight times. The six aconitine alkaloids concentration in perfusate were determined by HPLC-MS/MS. The concentration-time curves were plotted, and the pharmacokinetic parameters were calculated and analyzed by SPSS. The effects of Paeoniae Radix Alba on transdermal permeation role of six aconitine alkaloids in herb couple of Paeoniae Radix Alba-Aconiti Radix Cocta were investigated. According to the results, Tmax of the three mono-ester aconitum alkaloids of Aconiti Radix Cocta combined with Paeoniae Radix Alba groups were shortened, meanwhile, Cmax and AUC of benzoylaconine and benzoylhypaconine were increased. However, AUC of the three diester-type alkaloids were reduced, with Tmax of hypaconitine prolonged and Cmax lowered. The study suggested that the combined administration of Aconiti Radix Cocta and Paeoniae Radix Alba promoted the transdermal permeation of mono-ester aconitum alkaloids, and inhibited the absorption of parts of diester-type alkaloids. This study proved the decreasing toxicity and increasing efficacy of the combination of Aconiti Radix Cocta and Paeoniae Radix Alba on the transdermal permeation, and provided a reference for studies on the prescription combination regularity and relevant practices.
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Objective: To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats. Methods: A total of 60 Wister rats were included in the study and divided into control group (n = 10), model group (n = 25) and treatment group (n = 25). Model group and treatment group received intraperitoneal injection of endotoxin (ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL. Five rats were taken out of model group and treatment group respectively at 1 h (T1), 6 h (T2), 12 h (T3), 24 h (T4) and 48 h (T5), for intraperitoneal injection of ET 30 mg/kg. Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET. For three groups, 5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points. Concentrations of serum tumor necrosis factor α and ET-1 were determined by using ELISA. The renal pathologic changes were observed under the microscope. Results: Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5 (P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5 (P < 0.05). At T2-T5, blood urea nitrogen levels in model group and treatment group were significantly higher than control group (P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5 (P < 0.05). Concentrations of serum tumor necrosis factor α in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5 (P < 0.05). Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group at T1-T4 were significantly lower than model group (P < 0.05). Rats in control group showed no swelling or hyperemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells. Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition, hyperemia and angiectasis in glomerulus, degenerative opacities and vacuolar degeneration, and maximized injury were observed at T4. Injury in renal tissue in treatment group was significantly milder than model group. Conclusions: Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.
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<p><b>OBJECTIVE</b>To observe the evolutionary tendency of brain derived neurotrophic factor (BDNF) of the limbic system in post-stroke model rats and the intervention effect of Yinao Jieyu Recipe (YJR).</p><p><b>METHODS</b>Male Wistar rats were randomly divided into the normal control group (n =6), the sham-operation group (n =7), the multiple cerebral infarction (MCI) group (n =10), the post-stroke depression (PSD) group (n =10), the Chinese medicine (CM) treatment group (n =10), and the Western medicine (WM) treatment group (n =10) according to random digit table after open-field testing. Rats in the normal control group were routinely fed. 0. 3 mL normal saline was intravenously pushing from the external carotid artery to rats in the sham-operation group, and distilled water administered to them by gastrogavage. Each dose allogenic microthrombi were in vitro pushed to rats in the rest groups from the external carotid artery. The PSD model was duplicated by 21-day chronic unpredictable mild stress (CUMS) and single cage feeding in the PSD group 7 days after surgery. After preparing models rats in the CM group and the WM group were administered with YJR and Nimodipine respectively for 4 successive weeks. Changes of BDNF and the intervention effect of YJR were observed at week 1, 2, and 4 after intervention.</p><p><b>RESULTS</b>Immunohistochemical results of BDNF showed, compared with the normal control group, expression levels of BDNF in the hippocampus, hypothalamus, and amygdala decreased in the MCI group at week 2 and 4 (P <0. 01 , P <0. 05) ; expression levels of BDNF in each part decreased in the PSD group at week 1-4 (P <0.01). Compared with the MCI group, expression levels of BDNF in each part decreased in the PSD group at week 1-4 (P <0. 01). Compared with the PSD group, expression levels of BDNF in each part increased in the CM group at week 1-4 (P <0. 01).</p><p><b>CONCLUSION</b>BDNF changes existed in post-stroke model rats, and YJR could slow down this progress.</p>
Subject(s)
Animals , Male , Rats , Amygdala , Brain-Derived Neurotrophic Factor , Metabolism , Depression , Depressive Disorder , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Hippocampus , Models, Animal , Rats, Wistar , Stroke , Drug TherapyABSTRACT
OBJECTIVE@#To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.@*METHODS@#A total of 60 Wister rats were included in the study and divided into control group (n = 10), model group (n = 25) and treatment group (n = 25). Model group and treatment group received intraperitoneal injection of endotoxin (ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL. Five rats were taken out of model group and treatment group respectively at 1 h (T1), 6 h (T2), 12 h (T3), 24 h (T4) and 48 h (T5), for intraperitoneal injection of ET 30 mg/kg. Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET. For three groups, 5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points. Concentrations of serum tumor necrosis factor α and ET-1 were determined by using ELISA. The renal pathologic changes were observed under the microscope.@*RESULTS@#Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5 (P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5 (P < 0.05). At T2-T5, blood urea nitrogen levels in model group and treatment group were significantly higher than control group (P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5 (P < 0.05). Concentrations of serum tumor necrosis factor α in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5 (P < 0.05). Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5 (P < 0.05) while the levels in treatment group at T1-T4 were significantly lower than model group (P < 0.05). Rats in control group showed no swelling or hyperemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells. Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition, hyperemia and angiectasis in glomerulus, degenerative opacities and vacuolar degeneration, and maximized injury were observed at T4. Injury in renal tissue in treatment group was significantly milder than model group.@*CONCLUSIONS@#Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.
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AIM@#To investigate the chemical constituents and their biological activities of the aerial parts of Euphorbia tibetica.@*METHOD@#Compounds were isolated and purified by various chromatographic methods, and their structures were elucidated through the use of extensive spectroscopic techniques including 2D-NMR, the structures of compounds 5 and 6 were confirmed by single-crystal X-ray crystallography. Bioactivities of all the isolated compounds were evaluated by the MTT method on A549 and anti-angiogenesis assay.@*RESULTS@#One new compound, methyl 4-epi-shikimate-3-O-gallate (1), together with twenty-three known constituents (2-24) were isolated from the aerial parts of E. tibetica.@*CONCLUSION@#Compound 1 is new, and the other compounds were isolated from this plant for the first time. Compounds 5-7, 9, 11, 17, 18 and 20 exhibited inhibitory effects on the growth of human lung cancer cell A549 and compounds 5, 7, 12, 13, 17 and 19 showed anti-angiogenic effects in a zebrafish model.